Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans.Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality Morbidity and Mortality can refer to:
`kəsīt'): see blood. leukocyte or white blood cell or white corpuscle expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter 25 nm, geometric standard deviation In probability theory and statistics, the geometric standard deviation describes how spread out are a set of numbers whose preferred average is the geometric mean. If the geometric mean of a set of numbers is denoted as μg ~ 1.6), for 2 hr, in three separate protocols: 10 [micro]g/[m.sup.3] at rest, 10 and 25 [micro]g/[m.sup.3] with exercise, and 50 [micro]g/[m.sup.3] with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 [micro]g/[m.sup.3] UFPs with exercise. Peripheral venous blood venous blood n. Abbr. v Blood that has passed through the capillaries of various tissues other than the lungs, is found in the veins, in the right chambers of the heart, and in pulmonary arteries, and is usually dark red as a result of a was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry flow cytometry (flōˑ sī·t n.pl the largest of the white blood cells. They have one nucleus and a large amount of grayish-blue cytoplasm. Develop into macrophages and both consume foreign material and alert T cells to its presence. and CD18 and CD49d on granulocytes Granulocytes White blood cells. Mentioned in: Blood Donation and Registry granulocytes (granˑ·y . There were also concentration-related reductions in blood monocytes, basophils, and eosinophils Eosinophils A leukocyte with coarse, round granules present. Mentioned in: Histiocytosis X eosinophils and increased lymphocyte lymphocyte: see blood; immunity. lymphocyte Type of leukocyte fundamental to the immune system, regulating and participating in acquired immunity. Each has receptor molecules on its surface that bind to a specific antigen. expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 [micro]g/[m.sup.3] UFPs reduced expression of CD 11 b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD[4.sup.+] T cells T cells A type of white blood cell produced in the thymus gland. T cells are an important part of the immune system. Infants born with an underdeveloped or absent thymus do not have a normal level of T cells in their blood. , basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood peripheral blood Cardiology Blood circulating in the system/body leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed. Key words: blood leukocytes, human, monocytes, ultrafine particles. Environ Health Perspect 114:51-58 (2006). doi:10.1289/ehp.7962 available via http://dx.doi.org/[Online 20 September 2005] ********** Exposure to particulate matter (PM) air pollution is associated with increased respiratory and cardiovascular morbidity and mortality (Peters et al. 2000, 2001a; Pope et al. 2004). Plausible mechanisms explaining the cardiovascular effects of particle exposure have not been clearly defined (Utell et al. 2002). However, recent studies provide evidence that PM exposure is associated with systemic inflammation and changes in vascular function that have been implicated im·pli·cate tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates 1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot. 2. in the pathophysiology pathophysiology /patho·phys·i·ol·o·gy/ (-fiz?e-ol´ah-je) the physiology of disordered function. path·o·phys·i·ol·o·gy n. 1. of cardiovascular disease Cardiovascular disease Disease that affects the heart and blood vessels. Mentioned in: Lipoproteins Test cardiovascular disease , providing clues to possible mechanisms. PM exposure has been associated with increased systolic blood pressure Systolic blood pressure Blood pressure when the heart contracts (beats). Mentioned in: Hypertension (Ibald-Mulli et al. 2001), plasma viscosity (Peters et al. 1997a), C-reactive protein C-Reactive Protein Definition C-reactive protein (CRP) is a protein produced by the liver and found in the blood. Purpose C-reactive protein is not normally found in the blood of healthy people. (Peters et al. 2001b), fibrinogen Fibrinogen The major clot-forming substrate in the blood plasma of vertebrates. Though fibrinogen represents a small fraction of plasma proteins (normal human plasma has a fibrinogen content of 2–4 mg/ml of a total of 70 mg protein/ml), its conversion (Pekkanen et al. 2000), and release of leukocytes from the bone marrow (Mukae et al. 2001; Tan et al. 2000). Increases in ambient concentrations of PM were associated with increased blood leukocyte and platelet counts, as well as fibrinogen (Schwartz 2001). Brook et al. (2002) found evidence for systemic vasoconstriction vasoconstriction /vaso·con·stric·tion/ (-kon-strik´shun) decrease in the caliber of blood vessels.vasoconstric´tive va·so·con·stric·tion n. in resting human subjects exposed to concentrated ambient air particles and ozone. Ultrafine particles (UFPs), defined as particles with a diameter < 100 nm, have been hypothesized as contributors to cardiovascular effects of PM (Seaton et al. 1995) because, compared with fine particles at similar mass concentrations, they have greater pulmonary deposition efficiency (Chalupa
A chalupa is a kind of tostada platter in Mexican cuisine. et al. 2004; Daigle et al. 2003), induce more pulmonary inflammation (Li et al. 1999; Oberdorster et al. 1995), have enhanced oxidant oxidant /ox·i·dant/ (ok´si-dant) the electron acceptor in an oxidation-reduction (redox) reaction. ox·i·dant n. See oxidizer. capacity (Brown et al. 2001; Li et al. 2003), have a higher propensity to penetrate the epithelium and reach interstitial sites (Stearns et al. 1994), and may even enter the systemic circulation systemic circulation n. Circulation of blood throughout the body through the arteries, capillaries, and veins, which carry oxygenated blood from the left ventricle to various tissues and return venous blood to the right atrium. in humans (Nemmar et al. 2002; Oberdorster et al. 2002). Relatively few epidemiologic studies have examined the health effects of UFP UFP United Federation of Planets (Star Trek) UFP Union des Forces Progressistes (French: Union of the Forces Progressists, Quebec provincial party) UFP URL Filtering Protocol exposure because most ambient air monitoring measures particle mass, and there is relatively poor correlation between particle mass (dominated by fine particles) and particle number (dominated by UFPs). However, a recent study in Erfurt, Germany, found associations between ambient UFPs and mortality (Wichmann et al. 2000). In a study of patients with stable coronary artery disease coronary artery disease, condition that results when the coronary arteries are narrowed or occluded, most commonly by atherosclerotic deposits of fibrous and fatty tissue. (Pekkanen et al. 2002), investigators performed repeated exercise tests concurrent with monitoring of ambient particle mass and number counts. Significant independent effects were found for both fine particles and UFPs on the degree of ST-segment depression on the electrocardiogram electrocardiogram /elec·tro·car·dio·gram/ (-kahr´de-o-gram?) a graphic tracing of the variations in electrical potential caused by the excitation of the heart muscle and detected at the body surface. during exercise. Asthma, a disease characterized by airway inflammation, confers an increased risk for PM health effects (Atkinson et al. 2001; Lipsett et al. 1997; Tolbert et al. 2000). There is evidence for activation of lung leukocytes and pulmonary vascular endothelium endothelium /en·do·the·li·um/ (-the´le-um) pl. endothe´lia the layer of epithelial cells that lines the cavities of the heart, the serous cavities, and the lumina of the blood and lymph vessels. in subjects with asthma, particularly during exacerbations (Ohkawara et al. 1995). Activation of T-lymphocytes with production of "type 2" inflammatory cytokines Cytokines Chemicals made by the cells that act on other cells to stimulate or inhibit their function. Cytokines that stimulate growth are called "growth factors. drives the recruitment and retention of eosinophils in the airway, which contribute to the chronic epithelial injury characteristic of this disease (Corrigan and Kay 1990; Wilson et al. 1992). Treatment with inhaled corticosteroids Corticosteroids, Inhaled Definition Inhaled corticosteroids are glucocorticoids (a class of steroid hormones that are synthesized by the adrenal cortex and have anti-inflammatory activity) formulated to be used in the respiratory tract and lungs. reduces expression of activation markers CD25 and human leukocyte antigen human leukocyte antigen n. Abbr. HLA A gene product of the major histocompatibility complex; these antigens have been shown to have a strong influence on human allotransplantation, transfusions in refractory patients, and certain disease (HLA HLA human leukocyte antigens. HLA abbr. human leukocyte antigen HLA (human leuckocyte antigen) )-DR in lung lymphocytes Lymphocytes Small white blood cells that bear the major responsibility for carrying out the activities of the immune system; they number about 1 trillion. and also reduces HLA-DR expression in blood lymphocytes (Wilson et al. 1994). In asthma, blood CD[4.sup.+] T cells express increased mRNA for interleukin interleukin Any of a class of naturally occurring proteins important in regulation of lymphocyte function. Several known types are recognized as crucial constituents of the body's immune system (see immunity). (IL)-4, IL-5, and granulocyte granulocyte /gran·u·lo·cyte/ (gran´u-lo-sit?) granular leukocyte.granulocyt´ic band-form granulocyte band cell. gran·u·lo·cyte n. macrophage macrophage /mac·ro·phage/ (mak´ro-faj) any of the large, mononuclear, highly phagocytic cells derived from monocytes that occur in the walls of blood vessels (adventitial cells) and in loose connective tissue (histiocytes, phagocytic colony stimulating factor colony stimulating factor n. A hormone produced in the cells lining the blood vessels that stimulates the bone marrow to synthesize white blood cells. , and IL-5 mRNA expression correlates with asthma severity and eosinophilia eosinophilia /eo·sin·o·phil·ia/ (e?o-sin?o-fil´e-ah) abnormally increased eosinophils in the blood. e·o·sin·o·phil·i·a n. An increase in the number of eosinophils in the blood. (Corrigan et al. 1995). Allergen allergen /al·ler·gen/ (al´er-jen) an antigenic substance capable of producing immediate hypersensitivity (allergy).allergen´ic pollen allergen challenge in subjects with asthma causes a reduction in blood Cd[4.sup.+] T cells (Walker et al. 1992) and an increase in airway Cd[4.sup.+] cells (Virchow et al. 1995). UFP exposure may worsen asthma by further shifting lymphocyte responses to the type 2 phenotype, by further activating resident lymphocytes, by increasing the likelihood that lymphocytes will encounter antigen, and/or by increasing penetration of allergen through an injured epithelium. We have initiated controlled exposure studies with carbon UFPs in humans, as a surrogate for environmental UFPs, demonstrating that UFPs have a high pulmonary deposition efficiency in healthy subjects (Daigle et al. 2003), which is further increased in subjects with asthma (Chalupa et al. 2004). Exposure to 50 [micro]g/[m.sup.3] carbon UFPs caused a reduction in the pulmonary diffusing capacity dif·fus·ing capacity n. The capacity of the alveolocapillary membrane to transfer gas. diffusing capacity the rate at which a gas diffuses across the alveolar-capillary membrane per unit difference in the partial pressure of the for carbon monoxide carbon monoxide, chemical compound, CO, a colorless, odorless, tasteless, extremely poisonous gas that is less dense than air under ordinary conditions. It is very slightly soluble in water and burns in air with a characteristic blue flame, producing carbon dioxide; (Pietropaoli et al. 200%) associated with reductions in the systemic vascular response to increased flow (Pietropaoli et al. 2004a), without significant effects on symptoms, airway inflammation, lung function, or markers of blood coagulation (Pietropaoli et al. 2004c). We hypothesized that inhalation of UFPs alters vascular function, detectable as alterations in blood leukocyte distribution, activation, and expression of adhesion molecules. We further hypothesized that people with asthma, who have airway and systemic inflammation at baseline as well as enhanced UFP deposition, have enhanced susceptibility to these vascular effects. In this article we present detailed analyses of venous blood leukocytes from subjects participating in four separate studies involving carbon UFP exposure: three protocols with varying exposure concentrations in healthy subjects, and one protocol with asthmatic subjects. Some data in this article have been presented previously in abstract form (Frampton et al. 2004). Materials and Methods Subjects. Written, informed consent was obtained from all subjects, and the studies were approved by the Research Subjects Review Board of the University of Rochester The University of Rochester (UR) is a private, coeducational and nonsectarian research university located in Rochester, New York. The university is one of 62 elected members of the Association of American Universities. . Fifty-six never-smoking subjects 18-40 years of age (40 healthy and 16 with asthma) participated and were paid a stipend. Subjects were not studied within 6 weeks of a respiratory infection. Healthy subjects were required to have normal spirometry Spirometry The measurement, by a form of gas meter, of volumes of gas that can be moved in or out of the lungs. The classical spirometer is a hollow cylinder (bell) closed at its top. , a normal 12-lead electrocardiogram, and no history of chronic respiratory disease. Inclusion criteria for subjects with asthma have been reported previously (Chalupa et al. 2004). These criteria included a consistent clinical history, and either a significant bronchodilator bronchodilator /bron·cho·di·la·tor/ (-di´la-ter) 1. expanding the lumina of the air passages of the lungs. 2. an agent which causes dilatation of the bronchi. response or airway hyper-responsiveness to methacholine. The severity was consistent with mild intermittent to moderate persistent asthma (National Institutes of Health 1997). Subjects with forced expiratory volume forced expiratory volume n. Abbr. FEV The maximum volume of air that can be expired from the lungs in a specific time interval when starting from maximum inspiration. in 1 sec (FE[V.sub.1]) < 70% of predicted at baseline screening, or with > 20% reduction in FE[V.sub.1] after the screening exercise, were excluded. Study design. Each study used a crossover design in which each subject was exposed to filtered air and to UFPs, so that each subject served as his or her own control. Within each study, the order of air/UFP exposure was randomized ran·dom·ize tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es To make random in arrangement, especially in order to control the variables in an experiment. , and the randomization randomization (ranˈ·d Table 1 provides details of each study protocol. The first, UPREST, involved 12 (six female) subjects exposed at rest to approximately 10 [micro]g/[m.sup.3] UFPs or filtered air for 2 hr. The second study protocol, UPDOSE, involved 12 subjects (six female) with three 2-hr exposures with exercise for each subject: approximately 10 [micro]g/[m.sup.3] UFPs, approximately 25 [micro]g/[m.sup.3] UFPs, and filtered air. Subjects exercised on a bicycle ergometer ergometer /er·gom·e·ter/ (er-gom´e-ter) a dynamometer. bicycle ergometer an apparatus for measuring the muscular, metabolic, and respiratory effects of exercise. for 15 min of each half hour at an intensity adjusted to increase the minute ventilation to approximately 20 L/mini/[m.sup.2] body surface area. For safety reasons, the order of exposure was randomized in a restricted fashion, so that each subject received the 10-[micro]g/[m.sup.3] exposure before the 25-[micro]g/[m.sup.3]. The third protocol, UP50, involved 16 healthy subjects (eight female) exposed to approximately 50 [micro]g/[m.sup.3] UFPs and air for 2 hr, with intermittent exercise as in the UPDOSE protocol. The final protocol, UPASTHMA, involved 16 subjects with asthma (eight female) exposed to approximately 10 [micro]g/[m.sup.3] UFPs and air for 2 hr, with intermittent exercise as in the UPDOSE protocol. All exposures were separated by at least 2 weeks. Exposures to either filtered air or UFPs were administered by mouthpiece (with nose clip) for 2 hr, interrupted by a 10-min break after the first hour. Before and at 0, 3.5, and 21 hr after exposure, blood pressure, heart rate, and oxygen saturation oxygen saturation sO2 The O2 concentration of blood expressed as a ratio of its total O2-carrying capacity; the OS is a measure of the utilization of O2 transport capacity; sO2 by pulse oximetry pulse oximetry Oxygen saturation measurement, SaO Critical care A method used to determine the O2 saturation–SaO2 and desaturation of blood in a continuous noninvasive fashion, through the noninvasive assessment of arterial Hb-bound were measured, and blood was drawn from an antecubital vein. For UP50 and UPASTHMA, measurements were also obtained 45 hr after exposure. Exposure system. The rationale and design of the exposure facility have been described in detail elsewhere (Chalupa et al. 2002). Briefly, particles [count median diameter ~ 25 nm, geometric standard deviation ~ 1.6] were generated in an argon argon (är`gŏn) [Gr.,=inert], gaseous chemical element; symbol Ar; at. no. 18; at. wt. 39.948; m.p. −189.2°C;; b.p. −185.7°C;; density 1.784 grams per liter at STP; valence 0. atmosphere using an electric spark discharge between two graphite electrodes, and then deionized de·i·on·ize tr.v. de·i·on·ized, de·i·on·iz·ing, de·i·on·iz·es To remove ions from (a solution) using an ion-exchange process. de·i and diluted with filtered air to the desired concentration. Particle number, mass, and size distribution were monitored on both the inspiratory in·spi·ra·to·ry adj. Of, relating to, or used for the drawing in of air. inspiratory pertaining to or used in the inspiration of air into the lungs. and expiratory ex·pi·ra·to·ry adj. Of, relating to, or involving the expiration of air from the lungs. expiratory relating to or employed in the expiration of air from the lungs. sides of the subject. Electronic integration of a pneumotachograph pneu·mo·tach·o·graph n. An apparatus for recording the rate of airflow to and from the lungs. Also called pneumotachometer. pneumotachograph an instrument for recording the velocity of respired air. signal provided tidal volume tidal volume n. The volume of air inspired or expired in a single breath during regular breathing. Also called tidal air. tidal volume, n , respiratory frequency, and minute ventilation measurements. Air for the control exposures, and for dilution of the particles, was passed through charcoal and high-efficiency particle filters and was essentially free of particles (0-10 particles/[cm.sup.3]). Blood leukocyte immunofluorescence Immunofluorescence A technique that uses a fluorochrome to indicate the occurrence of a specific antigen-antibody reaction. The fluorochrome labels either an antigen or an antibody. analysis. Fresh heparinized whole blood was stained with three monoclonal antibodies: the marker of interest (Table 2) conjugated conjugated adj. Conjugate. estrogens, conjugated Warning - Hazardous drug! C.E.S. to fluorescein isothiocyanate, CD14 conjugated to phycoerythrin phy·co·er·y·thrin n. A red phycobilin occurring especially in the cells of red algae. Noun 1. phycoerythrin - red pigment in red algae , and CD45 conjugated to pericidin chlorophyll protein. This permitted determination of the relative expression of adhesion molecules and other markers separately on polymorphonuclear leukocytes polymorphonuclear leukocytes (pol´ēmôr´fōnoo´klē n. (PMNs), eosinophils, lymphocytes, and monocytes. The appropriate isotype i·so·type n. An antigenic marker that occurs in all members of a subclass of an immunoglobulin class. i control antibodies were run with each experiment to assist in appropriate gate setting. The adhesion markers shown in Table 2 were measured in each of the study protocols, except for CD18, which was measured in UP50 and UPASTHMA only. Red blood cells Red blood cells Cells that carry hemoglobin (the molecule that transports oxygen) and help remove wastes from tissues throughout the body. Mentioned in: Bone Marrow Transplantation red blood cells were lysed and cells were analyzed on a FACScan flow cytometer (BD Bioscience, San Jose, CA) equipped with a 15-mW argon ion laser emitting at 488 nm. Ten thousand events were collected from each sample in list mode. Standardized fluorescent microbeads (Quantium 24P and 25P; Bangs Laboratories, Fishers, IN) were run with each experiment to convert mean channel numbers to molecules of equivalent soluble fluoro-chrome (MESF MESF Mobile Electronics and Security Federation (UK trade association) MESF Maritime Expeditionary Security Force MESF Minimum Engineered Safety Feature ) (Gavras et al. 1994). This provided a correction for minor day-to-day instrument variations in fluorescence detection. Total and differential blood leukocyte and platelet counts were performed in the clinical laboratories of Strong Memorial Hospital, using an automated analyzer (Celldyne 4000; Abott Laboratories, Santa Clara, CA). Data handling and statistical methods. Data were entered on a desktop computer using Microsoft Excel and analyzed using SAS (1) (SAS Institute Inc., Cary, NC, www.sas.com) A software company that specializes in data warehousing and decision support software based on the SAS System. Founded in 1976, SAS is one of the world's largest privately held software companies. See SAS System. (SAS Institute Inc., Cary, NC). UPREST, UPASTHMA, and UP50 used a standard, two-period crossover design in which each subject received both particles and air. Equal numbers of males and females were included. The order of presentation was randomized separately for each sex, with half of each group of subjects receiving each of the two possible orders. UPDOSE used a three-period crossover design in which each subject received air and both 10-[micro]g/[m.sup.3] and 25-[micro]g/[m.sup.3] concentrations of particles. There were then three possible exposure sequences, depending on where in the sequence the air exposure was placed. Equal numbers of subjects were randomly assigned to each sequence. Repeated-measures analysis of variance (ANOVA anova see analysis of variance. ANOVA Analysis of variance, see there ) was used (Wallenstein and Fisher 1977), with order of presentation as a between-subjects factor, with exposure and time as within-subject factors. The analysis included tests for period and carryover effects, although the latter were expected to be minimal because of the nature of the exposures and the length of the washout washout to disperse or empty by flooding with water or other solvent. medullary solute washout a syndrome in which the relative hyperosmolarity of the renal medulla is reduced due to an excessive loss of sodium and chloride from period. In cases where carryover effects were significant, first-period data were examined separately (Jones and Kenward 1989). Each ANOVA included an examination of residuals as a check on the required assumptions of normally distributed errors with constant variance. If these assumptions were not satisfied, data transformations (e.g., square-root transformation for cell counts) were considered. A p-value of 0.05 was required for statistical significance. Data are shown as mean [+ or -] SE, unless otherwise indicated. Results Exposure data and subject characteristics. Table 3 shows the exposure parameters and subject characteristics for each protocol. Most of the subjects with asthma were atopic atopic /atop·ic/ (a-top´ik) (ah-top´ik) 1. ectopic. 2. pertaining to atopy; allergic. atopic 1. displaced; ectopic. 2. pertaining to atopy. (15 of 16), and most (11 of 16) were not on inhaled steroids, long-acting bronchodilators Bronchodilators Definition Bronchodilators are medicines that help open the bronchial tubes (airways) of the lungs, allowing more air to flow through them. , or leukotriene inhibitors Leukotriene Inhibitors Definition Leukotriene inhibitors are prescription medications that treat asthma and some allergies by blocking the formation or activity of leukotrienes—small mediator chemicals produced by cells in the body. . All subjects completed every exposure; men and women did not differ in the achieved minute ventilation, adjusted for body surface area. There were no significant effects of UFP exposure on ventilatory parameters or pulmonary function; these results, and UFP deposition, have been published previously (Daigle et al. 2003). The UPREST protocol, with exposures at rest to 10 [micro]g/[m.sup.3] UFPs, showed no convincing differences between particle and air exposure for leukocyte expression of adhesion molecules or total and differential leukocyte counts. There were rare statistically significant comparisons, but the significance levels were modest, and the data did not suggest a consistent biologic response. Overall, exposure to 10 [micro]g/[m.sup.3] UFPs at rest had no significant effects on blood leukocytes. Findings from the three studies involving exercise are described below. Blood leukocyte expression of adhesion molecules. In these studies, quantitative surface expression of molecules that mediate leukocyte-endothelial interactions served as an indirect indicator of exposure effects on pulmonary vascular endothelial endothelial /en·do·the·li·al/ (-the´le-al) pertaining to or made up of endothelium. Endothelial A layer of cells that lines the inside of certain body cavities, for example, blood vessels. function. The use of flow cytometry with calibrated cal·i·brate tr.v. cal·i·brat·ed, cal·i·brat·ing, cal·i·brates 1. To check, adjust, or determine by comparison with a standard (the graduations of a quantitative measuring instrument): fluorescent beads allowed quantitation of small changes in surface marker density. Adhesion molecule expression for monocytes and PMNs in the three protocols involving exercise is shown in Tables 4-6. UPDOSE. UFP exposure caused a concentration-related reduction in monocyte monocyte /mono·cyte/ (mon´o-sit) a mononuclear, phagocytic leukocyte, 13µ to 25µ in diameter, with an ovoid or kidney-shaped nucleus, and azurophilic cytoplasmic granules. expression of CD54 [intercellular intercellular /in·ter·cel·lu·lar/ (-sel´u-lar) between or among cells. in·ter·cel·lu·lar adj. Located among or between cells. adhesion molecule-1 (ICAM-1) (exposure effect, p = 0.0012); Figure 1]. Expression increased after exposure to filtered air and decreased with 25 [micro]g/[m.sup.3] UFPs, with differences resolving by 21 hr after exposure. Expression of CD62L showed a significant exposure-sex interaction (p = 0.0006; data not shown), with expression increasing in females but decreasing in males relative to air exposure. However, these findings lacked a clear concentration response. [FIGURE 1 OMITTED] UP50. Exposure to 50 [micro]g/[m.sup.3] UFPs also reduced expression of CD54 on monocytes (Figure 2A, B), but to a greater extent in males (exposure-sex interaction, p = 0.025). The percentage of monocytes expressing CD54 was also reduced (p = 0.035; data not shown). UFP exposure persistently blunted the airrelated increase in CD 18 expression on monocytes (p = 0.0002; Figure 2C). Expression of CD18 was also reduced on PMNs (Figure 2D), and ANOVA indicated significantly increased CD11a expression on PMNs (exposure-time interaction, p = 0.037; data not shown). [FIGURE 2A-4D OMITTED] UPASTHMA. As expected, we found baseline differences between healthy and asthmatic subjects in leukocyte expression of adhesion molecules; these data are shown in Table 7. For example, monocyte expression of CD1 lb, CD54, and CD62L was higher in subjects with asthma than in healthy subjects. In subjects with asthma, exposure to 10 [micro]g/[m.sup.3] UFPs reduced expression of CD11b on blood monocytes (p = 0.029; Figure 3A) and also reduced expression on eosinophils (p = 0.015; Figure 3B). Expression of CD62L on PMNs increased in males but not females (exposure-sex interaction, p = 0.011; Figure 3C,D). Expression of CD54 on PMNs decreased, with the greatest difference from control at 45 hr after exposure (exposure-time interaction, p = 0.031; data not shown). [FIGURE 3A-3D OMITTED] Lymphocyte subsets and activation. There was evidence for increased activated T cells after UFP exposure in healthy subjects. In UPDOSE, CD25 expression on CD[3.sup.+] T cells increased in females, but not in males, early after exposure to 25 [micro]g/[m.sup.3] UFPs (exposure-sex interaction, p = 0.002; Figure 4A, B). In UP50, exposure to 50 [micro]g/[m.sup.3] increased CD25 expression on T cells 0 hr after exposure (p = 0.001 by paired t-test at 0 hr after exposure; p = 0.085 by ANOVA; Figure 4C). There were no other changes in lymphocyte subsets in the healthy subjects. [FIGURE 4A-4C OMITTED] In UPASTHMA, CD[4.sup.+] Tcells decreased immediately after exposure to UFPs, compared with air (exposure-time interaction, p = 0.021; Figure 2D). There were no significant effects on other lymphocyte subsets or CD25 expression. However, the percentage of T-lymphocytes expressing the activation marker CD25 was higher in asthmatic subjects than in healthy subjects before exposure (UPASTHMA, 33.0 [+ or -] 3.3%, vs. UPDOSE, 27.0 [+ or -] 2.5%; p = 0.04). Overall, the data suggest that UFP exposure induces activation (healthy subjects) or sequestration sequestration In law, a writ authorizing a law-enforcement official to take into custody the property of a defendant in order to enforce a judgment or to preserve the property until a judgment is rendered. (subjects with asthma) of T-lymphocytes. Blood leukocyte and platelet counts. In each of the protocols involving exercise (UPDOSE, UP50, and UPASTHMA), consistent postexposure increases were seen in the total leukocyte count and the percentage of PMNs, with decreases in the percentage of eosinophils and monocytes. In the UPDOSE protocol, ANOVA showed a significant exposure-sex interaction for an effect on the percentage of blood monocytes (p = 0.0015). As shown in Figure 5A, B, in females monocytes decreased after exposure to 25 [micro]g/[m.sup.3] and did not return to baseline at 21 hr after exposure. This observation was confirmed when monocyte numbers were analyzed by flow cytometry, using light scatter and CD14 expression (overall effect of UFPs, p = 0.035; exposure-sex interaction, p = 0.002). A significant decrease in blood basophils in females was also seen with both UFP concentrations (exposure-sex interaction, p = 0.015; data not shown). [FIGURE 5A-5B OMITTED] Exposure to 50 [micro]g/[m.sup.3] UFPs caused small reductions in the percentage of eosinophils, with a larger effect in females (Figure 5C,D). There were no significant effects on the percentage of blood monocytes, PMNs, or basophils in this protocol. [FIGURE 5C-5D OMTTED] In subjects with asthma exposed to 10 [micro]g/[m.sup.3] UFPs, basophils decreased in both men and women at 0 and 3.5 hr after exposure to UFPs, compared with air exposure (exposure-time interaction, p = 0.02; data not shown). The percentage of blood eosinophils as determined by flow cytometry decreased 0 and 3.5 hr after exposure, with greater reductions after UFP exposure than after air (p = 0.049). UFP exposure did not change platelet counts in any of the exposure protocols. These data suggest that exposure to UFPs with exercise causes small changes in blood leukocyte differential counts in both healthy and asthmatic subjects. Discussion The objective of these studies was to determine whether inhalation of carbon UFPs has vascular effects in healthy subjects, and in subjects with asthma. We postulated that changes in blood leukocyte phenotype and expression of adhesion molecules would serve as a "window" on vascular inflammatory effects after inhalation challenge. Although the specific findings differed among the protocols, all three protocols with exercise showed UFP-associated reductions in expression of adhesion molecules on leukocytes, mainly ICAM-1 (CD54) and the [[beta].sub.2] integrins integrins (inˑ·t n.pl. CD11b and CD18. There were significant differences between healthy and asthmatic subjects in leukocyte expression of adhesion molecules, when measured before exposure (Table 7). For example, blood monocytes from subjects with asthma showed decreased expression of CD 11 a and increased expression of CD11b, CD49d, and CD54 relative to healthy subjects. This may reflect relative activation or priming of circulating leukocytes as a consequence of airway inflammation. In subjects with asthma, inhalation of UFPs reduced expression of CD11b on monocytes and eosinophils (Figure 3) and reduced CD54 expression on PMNs (Table 6). In addition, the data suggested subtle reductions relative to air exposure in the percentage of blood monocytes, eosinophils, and basophils. There was evidence for activation of CD[4.sup.+] T-lymphocytes in healthy subjects and transient reductions in CD[4.sup.+] T-cell numbers in asthmatic subjects. Sex interactions were seen for some of these changes. A summary of these findings is shown in Table 8. The findings provide evidence that inhalation of elemental carbon UFPs, with intermittent exercise, causes phenotypic alterations in blood leukocytes at concentrations as low as approximately 10 [micro]g/[m.sup.3] or approximately 2 x 106 particles/[cm.sup.3]. However, the overall nature and direction of the changes do not suggest increased systemic inflammation. This is consistent with the lack of evidence for airway or systemic inflammation that we have reported previously for these studies (Pietropaoli et al. 2004a, 20046. The reductions in leukocyte subsets and adhesion molecule expression seen in these studies suggest the possibility of leukocyte sequestration or margination margination /mar·gi·na·tion/ (mahr?ji-na´shun) accumulation and adhesion of leukocytes to the epithelial cells of blood vessel walls at the site of injury in the early stages of inflammation. in response to UFP exposure. The relative reductions in monocyte, basophil basophil /ba·so·phil/ (ba´so-fil) 1. any structure, cell, or histologic element staining readily with basic dyes. 2. , and eosinophil eosinophil /eo·sin·o·phil/ (e?o-sin´o-fil) a granular leukocyte having a nucleus with two lobes connected by a thread of chromatin, and cytoplasm containing coarse, round granules of uniform size. percentages may result from slightly prolonged transit time transit time the time required for ingesta to pass through the gastrointestinal tract; a shorter transit time is seen in conditions associated with gut hypermotility, such as diarrhea. Delayed passage from any cause results in a longer transit time. through the pulmonary circulation pulmonary circulation n. The passage of blood from the right ventricle through the pulmonary artery to the lungs and back through the pulmonary veins to the left atrium. after exposure to UFPs, possibly as a consequence of pulmonary vasoconstriction. The reductions in expression of the adhesion molecules CD54, CD11b, and CD18 are consistent with this hypothesis. Blood leukocytes normally marginate mar·gin·ate tr.v. mar·gin·at·ed, mar·gin·at·ing, mar·gin·ates 1. To provide with or be a margin to; border. 2. To add margin to (a stock portfolio). adj. in the lung, requiring several seconds to transit the pulmonary drculation (Doerschuk 2003). PMNs are larger than pulmonary capillaries and must deform in order to transit. The integrins CD1 la and CD11b are expressed as dimers with CD 18 and mediate blood leukocyte recruitment to areas of inflammation and injury via specific receptors on vascular endothdial cells. Activation of monocytes and PMNs increases expression of CD11b and CD18 and decreases cell deformability deformability /de·form·a·bil·i·ty/ (de-form?ah-bil´it-e) ability of cells to change shape when passing through narrow spaces, such as erythrocytes passing through the microvasculature. through actin polymerization polymerization Any process in which monomers combine chemically to produce a polymer. The monomer molecules—which in the polymer usually number from at least 100 to many thousands—may or may not all be the same. (Anderson et al. 2001), slowing transit time. Exercise increases pulmonary blood flow and decreases leukocyte transit time through the pulmonary circulation, leading to mobilization of the pulmonary leukocyte pool into the systemic vascular pool. Van Eeden et al. (1999) have shown that maximal exercise increases the blood leukocyte count and also increases expression of CD11b on peripheral blood PMNs, suggesting that cells expressing higher levels of CD11b preferentially marginate in the pulmonary circulation and are "flushed out" with exercise. Thus, our data are consistent with, but do not prove, increased retention of leukocytes expressing higher levels of adhesion molecules in the pulmonary vascular bed in response to UFP exposure. Pulmonary vasoconstriction in response to UFP exposure would be expected to delay leukocyte transit through the lung. We have reported (Pietropaoli et al. 2004b) that, in the UP50 protocol, UFP exposure caused reductions in the diffusing capacity for carbon monoxide, without effects on the forced vital capacity forced vital capacity n. Abbr. FVC Vital capacity measured with subject exhaling as rapidly as possible. forced vital capacity, n a measure of the maximum rate of exhalation. , consistent with reduced vascular perfusion or reduced ventilation/perfusion matching. We also reported preliminary findings (Pietropaoli et al. 2004a) of subtle but significant effects on systemic flow-mediated vascular dilatation dilatation /dil·a·ta·tion/ (dil?ah-ta´shun) 1. the condition, as of an orifice or tubular structure, of being dilated or stretched beyond normal dimensions. 2. the act of dilating or stretching. , and a decrease in blood nitrate levels, suggesting the vascular effects may result from decreased nitric oxide nitric oxide or nitrogen monoxide, a colorless gas formed by the combustion of nitrogen and oxygen as given by the reaction: energy + N2 + O2 → 2NO; m.p. −163.6°C;; b.p. −151.8°C;. availability. Batalha et al. (2002) have shown pulmonary vasoconstriction in rats exposed to concentrated ambient fine particles. Alternative mechanisms for reductions in leukocyte and their surface markers include a) direct effects of UFPs on blood leukocytes, reducing surface marker expression through shedding, redistribution, or internalization Internalization A decision by a brokerage to fill an order with the firm's own inventory of stock. Notes: When a brokerage receives an order they have numerous choices as to how it should be filled. ; b) indirect effects of mediators released by vascular endothelium, such as nitric oxide, which has anti-inflammatory properties (Lefer 1997), reduces endothelial expression of adhesion molecules via inhibition of nuclear factor [kappa]B activation, and reduces monocyte adhesion to endothelium (De Caterina et al. 1995); c) adsorption adsorption, adhesion of the molecules of liquids, gases, and dissolved substances to the surfaces of solids, as opposed to absorption, in which the molecules actually enter the absorbing medium (see adhesion and cohesion). of soluble cytokines, such as transforming growth factor- transforming growth factor–β1, –β2 Molecular biology Factors responsible for positive and negative autocrine growth regulation 13, onto the surface of the particles, reducing inflammatory effects (Kim et al. 2003); d) recruitment of immature leukocytes from the bone marrow in response to UFP inhalation, as has been suggested in previous studies of fine particle exposure (Tan et al. 2000); and e) selective toxicity of UFPs for activated blood leukocytes, inducing apoptosis of specific cell subsets. The two protocols with exercise in healthy subjects showed increased expression of CD25 on blood T-lymphocytes, and subjects with asthma showed a transient reduction in CD[4.sup.+] lymphocytes after UFP exposure. CD25 is the 0t-chain of the IL-2 receptor; IL-2 promotes lymphocyte proliferation. We found that lymphocyte CD25 expression was higher in subjects with asthma than in healthy subjects, confirming previous observations that people with asthma have a higher percentage of circulating activated T-lymphocytes (Corrigan and Kay 1990), which may explain why UFP exposure did not increase it further in these subjects. The rapid and transient nature of the reduction in CD[4.sup.+] T cells suggests redistribution or margination of cells, as postulated above for other blood leukocytes. The changes in response to carbon UFP exposure reported in these studies were generally small and would not be expected to adversely affect healthy and mildly asthmatic subjects similar to those studied. However, ambient UFPs contain reactive organic species and transition metals that may induce greater effects than those we observed. People with severely compromised cardiovascular status may experience adverse effects from even small changes in vascular homeostasis homeostasis Any self-regulating process by which a biological or mechanical system maintains stability while adjusting to changing conditions. Systems in dynamic equilibrium reach a balance in which internal change continuously compensates for external change in a feedback . Furthermore, prolonged, repeated exposures may hasten the progression of atherosclerosis, as has been suggested in an epidemiology study of fine particle exposure (Ktinzli et al. 2005). The UFP number concentrations used in these studies are higher than UFP background concentrations but are relevant to episodic levels seen in specific situations. UFPs are always present in ambient air, with background urban levels in the range of 40,000-50,000 particles/[cm.sup.3] or estimated mass concentrations of 3-4 [micro]g/[m.sup.3] (Peters et al. 1997b). Episodic increases have been documented to 300,000 particles/[cm.sup.3], or estimated to approximately 50 [micro]g/[m.sup.3] UFPs as an hourly average (Brand et al. 1991, 1992). Particle numbers inside a vehicle on a major highway reached 107 particles/[cm.sup.3] (Kittelson et al. 2001), comparable with the highest concentrations used in our studies. Although not specifically powered to detect sex differences, these studies were designed to include an analysis of sex interactions with the effects of UFP exposure. In the UPDOSE protocol, females showed greater decreases in blood monocytes (Figure 5A) and basophils and greater increases lymphocyte CD25 expression (Figure 4A) compared with males. Females also showed decreased eosinophils in the UP50 protocol (Figure 5C). In UPASTHMA, expression of L-selectin (CD62L) on PMNs was increased in males (Figure 3B). It is possible that males and females differ in their cardiovascular responses to particle exposure. There are known sex differences in leukocyte function and cardiovascular responses, based in part on hormonal influences. For example, females have a higher percentage of CD[4.sup.+] T cells and a higher CD[4.sup.+]:CD[8.sup.+] ratio than do males. Stimulated blood monocytes from females produce more prosraglandin [E.sub.2] (Leslie and Dubey 1994) and less tumor necrosis tumor necrosis Death of tumor tissue, a common event in aggressive CAs in which the tumor rapidly outgrows its blood supply, resulting in tumor cell death. Cf Apoptosis. factor-[alpha] and IL-6 (Schwarz et al. 2000) than those from males. There are also sex differences in endothelial function and antioxidant antioxidant, substance that prevents or slows the breakdown of another substance by oxygen. Synthetic and natural antioxidants are used to slow the deterioration of gasoline and rubber, and such antioxidants as vitamin C (ascorbic acid), butylated hydroxytoluene defenses that may affect vascular response to inhaled challenge. However, we do not feel that these studies have convincingly established or excluded significant sex differences in responses to carbon UFPs. There are limitations to this study. First, our particles were laboratory-generated elemental carbon, without significant organic species, metals, oxides, nitrates, or sulfates. The findings of these studies may not be representative of exposure to ambient particles, which are a mix of ultrafine, fine, and coarse particles, with reactive organic species, metals, and oxidants in addition to elemental carbon. These and other chemical species may enhance pulmonary and vascular effects. Second, each protocol involved a fairly large number of measurements, and some statistically significant changes may have been chance related. Our approach was to consider results that showed consistency within and across protocols and to discount findings of isolated statistical significance that were not supported by other data. The observations of UFP effects on leukocyte distribution and surface marker expression meet those criteria. Conclusions Overall, the findings from these studies provide evidence that inhalation of carbon UFPs, with exercise, reduces peripheral blood monocytes, eosinophils, and basophils and reduces expression of some adhesion molecules on monocytes and PMNs. When considered in light of other evidence, the leukocyte changes may be a consequence of endothelial activation or vasoconstriction in the pulmonary and/or systemic circulation. This work was supported by contract 98-19 from the Health Effects Institute The Health Effects Institute (HEI) is a non-partisan, non-profit corporation specializing in research on the health effects of air pollution. It is headquartered in Charlestown, Massachusetts, USA. (HEI HEI Higher Education Institution (UK) HEI Health Effects Institute HEI Hautes Études Internationales HEI House Ear Institute HEI Healthy Eating Index HEI Hautes Etudes d'Ingénieur HEI High-Explosive Incendiary ); U.S. Environmental Protection Agency Environmental Protection Agency (EPA), independent agency of the U.S. government, with headquarters in Washington, D.C. It was established in 1970 to reduce and control air and water pollution, noise pollution, and radiation and to ensure the safe handling and (EPA EPA eicosapentaenoic acid. EPA abbr. eicosapentaenoic acid EPA, n.pr See acid, eicosapentaenoic. EPA, n. ) assistance agreements R826781-01 and R827354-01; grants RO1 ES011853, RR00044, and ES01247 from the National Institutes of Health; and grant 4913-ERTER-ES-99 from the New York State Energy Research and Development Authority The New York State Energy Research and Development Authority (NYSERDA) is a public benefit corporation that was created by the New York State Legislature in 1975. The purpose of the NYSERDA is to provide funding for the research of energy development. . Some of the research described in this article was conducted under contract to the HEI, an organization jointly funded by the U.S. EPA (assistance agreement X-812059) and automotive manufacturers. The contents of this article do not necessarily reflect the views of the HEI, nor do they necessarily reflect the policies of the U.S. EPA or of automotive manufacturers. REFERENCES Anderson GJ, Roswit WT, Holtzman MJ, Hogg JC, Van Eeden SF. 2001. Effect of mechanical deformation of neutrophils neutrophils (ner·ō·trōˑ·filz), n.pl white blood cells with cytoplasmic granules that consume harmful bacteria, fungi, and other foreign materials. on their CD18/ICAM-1-dependent adhesion. J Appl Physiol 91:1084-1090. Atkinson RW, Anderson HR, Sunyer J, Ayres J, Baccini M, Vonk JM, et al. 2001. Acute effects of particulate air pollution on respiratory admissions. Results from APHEA APHEA Australasian and Pacific Hansard Editors Association 2 project. Am J Respir Crit Care Med 164:1860-1866. Batalha JR, Saldiva PH, Clarke RW, Coull BA, Stearns RC, Lawrence J, et al. 2002. Concentrated ambient air particles induce vasoconstriction of small pulmonary arteries in rats. Environ Health Perspect 110:1191-1197. Brand P, Gebhart J, Below M, Georgi B, Heyder J. 1891. Characterization of environmental aerosols on Heligoland Island. Atmos Environ 25A:581-585. Brand P, Ruob K, Gebhart J. 1992. Performance of a mobile aerosol spectrometer for an in situ In place. When something is "in situ," it is in its original location. characterization of environmental aerosols in Frankfurt City. Atmos Environ 26A:2451-2457. Brook RD, Brook JR, Urch B, Vincent R, Rajagopalan S, Silverman F. 2002. Inhalation of fine particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults. Circuration 105:1534-1536. Brown DM, Wilson MR, MacNee W, Stone V, Donaldson K. 2001. Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress oxidative stress, n an imbalance of the prooxidant antioxidant ratio in which too few antioxidants are produced or ingested or too many oxidizing agents are produced. in the enhanced activity of ultrafines. Toxicol Appl Pharmacol 175:191-199. Chalupa DC, Morrow PE, Oberddrster G, Utell MJ, Frampton MW. 2004. Ultrafine particle deposition in subjects with asthma. Environ Health Perspect 112:879-882. Chalupa DF, Gibb FR, Morrow PE, 0berddrster G, Riesenfeld E, Gelein R, et al. 2002. A facility for controlled human exposures to ultrafine particles. In: Crucial Issues in inhalation Research--Mechanistic, Clinical and Epidemiologic (Heinrich U, Mohr U, eds). Washington, DC:ILSI ILSI International Life Sciences Institute ILSI Incorporated Law Society of Ireland Press, 241-253. Corrigan CJ, Harold Q, North J, Barkans J, Moqbel R, Durham S, et al. 1995. Peripheral blood CD4 but not CD6 T-lymphocytes in patients with exacerbation of asthma transcribe To copy data from one medium to another; for example, from one source document to another, or from a source document to the computer. It often implies a change of format or codes. and translate messenger HNA HNA Hereditary Neuralgic Amyotrophy HNA Hawaii Nurses Association HNA High North Alliance HNA Morioka, Japan - Hanamaki (Airport Code) HNA Hospice Nurses Association (now Hospice and Palliative Nurses Association) encoding cytokines which prolong eosinophil survival in the context of a Th2-type pattern: effect of glucocorticoid therapy Glucocorticoid therapy Treatment using corticoids that are anti-inflammatory and immunosuppressive. Mentioned in: Myelofibrosis . Am J Respir Cell Mol Biol 12:567-578. Corrigan CJ, Kay AB. 1990. CD4 T-lymphocyte activation in acute severe asthma. Am Rev Respir Dis 141:970-977. Daigle CC, Chalupa DC, Gibb FR, Morrow PE, Oberddrster G, Utell MJ, et al. 2003. Ultrafine particle deposition in humans during rest and exercise. Inhal Toxicol 15:539-552. De Caterina R, Libby P, Peng HB, Thannickal VJ, Rajavashisth TB, Gimbrone MAJ, et al. 1995. Nitric oxide decreases cytokine-induced endothelial activation. J Clio Invest 96:60-68. Boerschuk CM. 2003. Neutrophil neutrophil /neu·tro·phil/ (noo´tro-fil) 1. a granular leukocyte having a nucleus with three to five lobes connected by threads of chromatin, and cytoplasm containing very fine granules; cf. heterophil. 2. emigration emigration: see immigration; migration. in the lungs. In: Therapeutic Targets in Airway Inflammation (Eissa T, Huston DP, eds). New York New York, state, United States New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of :Marcel Dekker, 249-280. Frampton MW, Stewart JC, Oberdorster G, Pietropaoli AP, Morrow PE, Chalupa D, et al. 2004. Inhalation of carbon uitrafioe particles decreases expression of CD18 and CD11a on blood leukoeytes [Abstract]. Am J Respir Crit Care Med 169:A280. Gavras JB, Frampton MW, Ryan DH, Lew PC, Looney RJ, Cox C, et al. 1984. Expression of membrane antigens on human alveolar macrophages after exposure to nitrogen dioxide. Inhal Toxicol 6:633-646. Ibald-Mulli A, Stieber J, Wiehmann HE, Koenig W, Peters A. 2001. Effects of air pollution on blood pressure: a population-based approach. Am J Public Health 91:571-577. Jones B, Kenward MG. 1989. Design and Analysis of Crossover Trials. New York:Chapman and Hall Chapman and Hall was a British publishing house, founded in the first half of the 19th century by Edward Chapman and William Hall. Upon Hall's death in 1847, Chapman's cousin Frederic Chapman became partner in the company, of which he became sole manager upon the retirement of . Kim H, Liu X, Kobayashi T, Kohyama T, Wen F-Q, Romberger DJ, et al. 2003. Ultrafine carbon black particles inhibit human lung fibroblast-mediated collagen gel contraction. Am J Respir Cell Mol Biol 28:111-121. Kittelson DB, Watts WF, Johnson JP. 2001. Fine Particle (nanoparticle) Emissions on Minnesota Highways. Mn/DOT Report No. 2001-12. St. Paul, MN:Minnesota Department of Transportation The Minnesota Department of Transportation (Mn/DOT, pronounced "min-dot") oversees transportation by land, water, and air in the U.S. state of Minnesota. The cabinet-level agency is responsible for maintaining the state's trunk highway system (including state highways, U.S. . Kunzli N, Jerrett M, Mack WJ, Beckerman B, LaBree L, Gilliland F, et al. 2005. Ambient air pollution and atherosclerosis in Los Angeles. Environ Health Perspect 113:201-206. Lefer AM. 1997. Nitric oxide: nature's naturally occurring leukocyte inhibitor. Circulation 95:553-554. Leslie CA, Dubey DP. 1894. Increased PG[E.sub.2] from human monocytes isolated in the luteal phase luteal phase n. The portion of the menstrual cycle that begins with the formation of the corpus luteum and ends with the start of the menstrual flow, usually 14 days in length. of the menstrual cycle menstrual cycle n. The recurring cycle of physiological changes in the uterus, ovaries, and other sexual structures that occur from the beginning of one menstrual period through the beginning of the next. . Implications for immunity? Prostaglandins 47:41-54. Li N, Sioutas C, Cho A, Schmltz D, Misra C, Sempf J, et al. 2003. Ultrafine particulate pollutants induce oxidative stress and mitochondrial mitochondrial pertaining to mitochondria. mitochondrial RNAs a unique set of tRNAs, mRNAs, rRNAs, transcribed from mitochondrial DNA by a mitochondrial-specific RNA polymerase, that account for about 4% of the total cell RNA that damage. Environ Health Perspect 111:455-460. Li XY, Brown D, Smith S, MacNee W, Donaldson K. 1899. Short-term inflammatory responses following intratracheal instillation instillation /in·stil·la·tion/ (in?sti-la´shun) administration of a liquid drop by drop. instillation administration of a liquid drop by drop. of fine and ultrafine carbon black in rats. Inhal Toxicol 11:709-731. Lipsett M, Hurley S, Ostro B. 1997. Air pollution and emergency room visits for asthma in Santa Clara County, California Santa Clara County is a county located in the San Francisco Bay Area of the U.S. state of California. It is the primary site of Silicon Valley. As of 2000 it had a population of 1,682,585. The county seat is San Jose. . Environ Health Perspect 105:216-222. Mukae H, Vincent R, Quinlan K, English D, Hards J, Hogg JC, et al. 2001. The effect of repeated exposure to particulate air pollution (PMI See Private Mortgage Insurance. 0) on the bone marrow. Am J Respir Crit Care Med 163:201-209. National Institutes of Health. 1997. Expert Panel Report 2, Guidelines for the Diagnosis and Management of Asthma. NIH "Not invented here." See digispeak. NIH - The United States National Institutes of Health. Publication No. 97-4051. Bethesda, MD:National Institutes of Health, U.S. Department of Health and Human Services Noun 1. Department of Health and Human Services - the United States federal department that administers all federal programs dealing with health and welfare; created in 1979 Health and Human Services, HHS . Nemmar A, Hoet PH, Vanquickenborne B, Dinsdale D, Thomeer M, Hoylaerts MF, et al. 2002. Passage of inhaled particles into the blood circulation in humans. Circulation 105:411-414. Oberddrster G, Gelein RM, Ferin J, Weiss B. 1995. Association of particulate air pollution and acute mortality: involvement of ultrefine particles? Inhal Toxicol 7:111-124. Oberddrster G, Sharp Z, Attudorei V, Elder A, Gelein R, Lunts A, et al. 2002. Extrapulmonary transiocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health A 65:1531-1543. Ohkawara Y, Yamauchi K, Maruyama N, Hoshi H, Ohno I, Honrna M, et al. 1995. In situ expression of the cell adhesion molecules in bronchial bronchial /bron·chi·al/ (brong´ke-al) pertaining to or affecting one or more bronchi. bron·chi·al adj. Relating to the bronchi, the bronchial tubes, or the bronchioles. tissues from asthmatics with air flow limitation: in vivo in vivo /in vi·vo/ (ve´vo) [L.] within the living body. in vi·vo adj. Within a living organism. in vivo adv. evidence of VCAM-1/VLA-4 interaction in selective eosinophil infiltration. Am J Respir Cell Mol Biol 12:4-12. Pekkanen J, Brunner EJ, Anderson HR, Tiitanen P, Atkinson RW. 2000. Daily concentrations of air pollution and plasma fibrinogen in London. Occup Environ Med 57:818-822. Pekkanen J, Peters A, Hoek G, Tiittanen P, Brunekreef B, de Hartog J, et al. 2002. Particulate air pollution and risk of ST-segment depression during repeated submaximal exercise tests among subjects with coronary heart disease coronary heart disease: see coronary artery disease. coronary heart disease or ischemic heart disease Progressive reduction of blood supply to the heart muscle due to narrowing or blocking of a coronary artery (see atherosclerosis). . The exposure and risk assessment for fine and ultrafine particles in ambient air (ULTRA) study. Circulation 106:933-938. Peters A, Dockery DW, Muller JE, Mittleman MA. 2001a. Increased particulate air pollution and the triggering of myocardial infarction myocardial infarction: see under infarction. . Circulation 103:2810-2815. Peters A, Boring A, Wichmann H-E, Koenig W. 1997a. Increased plasma viscosity during an air pollution episode: a link to mortality? Lancet 349:1582-1587. Peters A, Frohlich M, Doring A, Immervoll T, Wichmann HE, Hutchinson WL, et al. 2001b. Particulate air pollution is associated with an acute phase response acute phase response n. A group of physiologic changes that occur shortly after the onset of an infection or other inflammatory process and include an increase in the blood level of various proteins, especially C-reactive protein, fever, and other in men; results from the MONICA-Augsburg Study. Eur Heart J 22:1198-1204. Peters A, Liu E, Verrier RL, Schwartz J, Gold DR, Mittleman M, et al. 2000. Air pollution and incidence of cardiac arrhythmia cardiac arrhythmia n. See cardiac dysrhythmia. Cardiac arrhythmia An irregular heart rate or rhythm. Mentioned in: Holter Monitoring, Stress Test cardiac arrhythmia . Epidemiology 11:11-17. Peters A, Wichmann HE, Tuch T, Heinrich J, Heyder J. 1997b. Respiratory effects are associated with the number of ultrafine particles. Am J Respir Crit Care Med 155:1376-1383. Pietropaoli AP, Delehanty JM, Perkins PT, Utell MJ, Oberddrster G, Hyde RW, et al. 2004e. Venous nitrate, nitrite nitrite Any salt or ester of nitrous acid (HNO2). The salts are inorganic compounds with ionic bonds, containing the nitrite ion (NO2−) and any cation. , and forearm blood flow after carbon ultrafine particle exposure in healthy human subjects [Abstract]. Am J Respir Crit Care Med 169:A883. Pietropaoli AP, Frampton MW, Hyde RW, Morrow PE, Oberddrster G, Cox C, et al. 2004b. Pulmonary function, diffusing capacity and inflammation in healthy and asthmatic subjects exposed to ultrafine particles. Inhal Toxicol 16(su ppl 1):59-72. Pietropaoli AP, Frampton MW, Oberddrster G, Cox C, Huang L-S L-S Left Side (medical exams) L-S Lockheed Sanders, Inc. , Marder V, et al. 2004c. Blood markers of coagulation coagulation (kōăg'y lā`shən), the collecting into a mass of minute particles of a solid dispersed throughout a liquid (a sol), usually followed by the precipitation or and inflammation in
healthy human subjects exposed to carbon ultrafine particles. In:
Effects of Air Contaminants on the Respiratory Tract--Interpretations
from Molecular to Meta analysis {Heinrich U, ed). Stuttgart:INIS INIS International Nuclear Information System (International Atomic Energy Agency)INIS International Neonatal Immunotherapy Study INIS Initializations Monographs, Fraunhofer IRB IRB See: Industrial Revenue Bond Verlag, 181-194. Pope CA III, Burnett RT, Thurston GD, Thun MJ, Calle EE, Krewski D, et al. 2004. Cardiovascular mortality and long-term exposure to particulate air pollution. Epidemiological evidence of general pathophysiological pathways of disease. Circulation 109:71-77. Schwartz J. 2001. Air pollution and blood markers of cardiovascular risk. Environ Health Perspect 109(suppl 3):405-409. Schwarz E, Schafer C, Bode JC, Bode C. 2000. Influence of the menstrual cycle on the LPS-induced cytokine Cytokine Any of a group of soluble proteins that are released by a cell to send messages which are delivered to the same cell (autocrine), an adjacent cell (paracrine), or a distant cell (endocrine). response of monocytes. Cytokine 12:413-416. Seaton A, MacNee W, Donaldson K, Godden D. 1995. Particulate air pollution and acute health effects. Lancet 345:176-178. Stearns RC, Murthy GGK GGK Giessener Graduiertenzentrum Kulturwissenschaften (German: Gießener Graduate Center for Cultural Studies) , Skornik W, Hatch V, Katler M, Godleski JJ. 1994. Detection of ultrafine copper oxide particles in the lungs of hamsters by electron spectroscopic spec·tro·scope n. An instrument for producing and observing spectra. spec tro·scop imaging. In: Proceedings of ICEM ICEM International Federation of Chemical, Energy, Mine and General Workers' UnionsICEM International Conference on Electrical Machines ICEM International Conference on Emergency Medicine ICEM Institut Cooperatif de l'Ecole Moderne 13-PARIS, 1994 (Jouffrey B, Colliex C, eds). Paris:Les Editions de Physique, 763-764. Tan WC, Qiu D, Liam BL, Ng TP, Lee Sri, van Eeden SF, et al. 2000. The human bone marrow response to acute air pollution caused by forest fires. Am J Respir Crit Care Med 161:1213-1217. Tolbert PE, Mulholland JA, Macintosh DL, Xu F, Baniels D, Devine OJ, et al. 2000. Air quality and pediatric pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children. pe·di·at·ric adj. Of or relating to pediatrics. emergency room visits for asthma in Atlanta, Georgia, USA. Am J Epidemiol 151:798-810. Utell MJ, Frampton MW, Zareba za·re·ba also za·ree·ba n. 1. An enclosure of bushes or stakes protecting a campsite or village in northeast Africa. 2. A campsite or village protected by such an enclosure. W, Devlin RB, Caseio WE. 2002. Cardiovascular effects associated with air pollution: potential mechanisms and methods of testing. Inhal Toxicol 14:1231-1247. van Eeden SF, Grantee An individual to whom a transfer or conveyance of property is made. In a case involving the sale of land, the buyer is commonly known as the grantee. grantee n. J, Hards JM, Moore B, Hogg JC. 1999. Expression of the cell adhesion molecules on leukocytes that demarginate during acute maximal exercise. J Appl Physiol 86:970-976. Virchow JCJ JCJ Japan Congress of Journalists , Walker C, Hafner D, Kortsik C, Werner P, Matthys H, et al. 1995. T cells and cytokines in bronchoalveolar lavage Bronchoalveolar lavage A way of obtaining a sample of fluid from the airways by inserting a flexible tube through the windpipe. Used to diagnose the type of lung disease. fluid after segmental allergen provocation in atopic asthma. Am J Respir Crit Care Med 151:960-958. Walker C, Bode E, Boer L, Hansel han·sel n. & v. Variant of handsel. TE, Blaser K, Virchow J-CJ. 1992. Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis 146:109-115. Wallenstein S, Fisher AC. 1977. Analysis of the two-period repeated measurements crossover design with application to clinical trials. Biometrics 30:261-269. Wichmann H-E, Spix C, Tuch T, Wdlke G, Peters A, Heinrich J, et al. 2000. Daily mortality and fine and ultrafine particles in Erfurt, Germany. Part I: Role of particle number end particle mass. Health Eft Inst Res Rep 98:1-86. Wilson JW, Djukanovic R, Howarth PH, Holgate ST. 1992. Lymphocyte activation in bronchoalveolar lavage and peripheral blood in atopic asthma. Am Rev Respir Dis 145:958-960. Wilson JW, Djukanovic R, Howarth PH, Holgate ST. 1994. Inhaled beclomethasone dipropionate bec·lo·meth·a·sone di·pro·pi·o·nate n. A corticosteroid usually used as an inhalant to treat asthma. beclomethasone dipropionate (bek´l downregulates airway lymphocyte activation in atopic asthma. Am J Respir Crit Care Med 149:86-90. The authors declare they have no competing financial interests. Address correspondence to M.W. Frampton, University of Rochester Medical Center The University of Rochester Medical Center (URMC), located in Rochester, New York, is one of the main campuses of the University of Rochester and comprises the university's primary medical education, research and patient care facilities. , 601 Elmwood Ave., Box 692, Rochester, NY 14642-8692 USA. Telephone: (585) 275-4861. Fax: (585) 273-1114. E-mail: mark_frampton@urmc.rochester.edu Mark W. Frampton, (1,2) Judith C. Stewart, (1) Gunter Oberdorster, (2) Paul E. Morrow, (2) David Chalupa, (1) Anthony P. Pietropaoli, (1) Lauren M. Frasier, (1) Donna M. Speers, (1) Christopher Cox, (3) Li-Shan Huang, (4) and Mark J. Utell (1,2) (1) Department of Medicine, and (2) Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York This article is about the city of Rochester in Monroe County. For the town in Ulster County, see Rochester, Ulster County, New York. Rochester, once known as The Flour City, and more recently as The Flower City or , USA; (3) Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University Johns Hopkins University, mainly at Baltimore, Md. Johns Hopkins in 1867 had a group of his associates incorporated as the trustees of a university and a hospital, endowing each with $3.5 million. Daniel C. , Baltimore, Maryland, USA; 4) Department of Biostatistics, University of Rochester School of Medicine, Rochester, New York, USA Received 25 January 2005; accepted 20 September 2005.
Table 1. Study design (mean [+ or -] SD).
UPREST UPDOSE
No. of subjects 12 12
Subject age 30.1 [+ or -] 8.9 26.9 [+ or -] 5.8
(years)
FE[V.sub.1] 103.8 [+ or -] 8.0 106.3 [+ or -] 16.6
(% predicted)
Nominala particle 0, 10 0, 10, 25
mass ([micro]g/
[m.sup.3])
Rest/exercise Rest Intermittent exercise
UP50 UPASTHMA
No. of subjects 16 16
Subject age 26.9 [+ or -] 6.5 23.0 [+ or -] 2.7
(years)
FE[V.sub.1] 102.8 [+ or -] 9.5 97.6 [+ or -] 5.0
(% predicted)
Nominala particle 0, 50 0, 10
mass ([micro]g/
[m.sup.3])
Rest/exercise Intermittent exercise Intermittent exercise
(a) The target mass concentration of UFPs for each protocol.
Table 2. Leukocyte markers measured in each protocol.
Cluster
designation Name Source (clone)
CD3 BD Bioscience (a) (SK7)
CD4 BD Bioscience (SK3)
CD8 BD Bioscience (SK1)
CD11 (a) Leukocyte GenTrak (b) (38) or
function Coulter (c) (25.3.1)
antigen-1
CD11 (b) Mac-1 Ancell (d) (ICRF44)
CD18 (e) Pharmigena (6.7) o
BD Bioscience (1-130)
CD25 Tac BD Bioscience (2A3)
CD49d Very late Serotec (f) (44H6)
antigen-
[alpha]4
CD54 Intercellular Southern Biotechnology (g)
adhesion (15.2)
molecule-1
CD62L L-selectin Coulter (DREG56) or
Pharmipen (DREG56)
Cluster
designation Description
CD3 Marker of T-lymphocytes
CD4 Marker of T-helper lymphocytes
CD8 Marker of T-cytotoxic lymphocytes
CD11 (a) Part of [[beta].sub.2] integrin adhesion molecule complex
CD11 (b) Subunit of complement receptor 3, part of [[beta].sub.2]
integrin adhesion molecule complex
CD18 (e) Part of [[beta].sub.2] adhesion molecule complex with
CD11a and CD11b
CD25 Epitope of IL-2 receptor, activation marker on
lymphocytes
CD49d Part of [[beta].sub.2] integrin adhesion molecule complex
CD54 Adhesion molecule
CD62L Adhesion molecule
(a) San Jose, CA. (b) Plymouth Meeting, PA. (c) Miami, FL. (e) Bayport,
MN. (e) Measured in UP50 and UPASTHMA only. (f) Raleigh, NC.
(g) Birmingham, AL.
Table 3. Exposure parameters (mean [+ or -] SD).
UPREST UPDOSE
Nominal particle 10 10
mass ([micro]g/
[m.sup.3])
Measured particle 10.00 [+ or -] 2.14 13.87 [+ or -] 4.02
mass ([micro]g/
[m.sup.3])
Particle number 1.88 [+ or -] 0.09 2.04 [+ or -] 0.07
(x [10.sup.6]
particles/
[cm.sup.3])
CMD(nm) 27.3 [+ or -] 2.5 25.2 [+ or -] 1.7
GSD 1.62 [+ or -] 0.02 1.60 [+ or -] 0.02
UPDOSE UP50
Nominal particle 25 50
mass ([micro]g/
[m.sup.3])
Measured particle 28.46 [+ or -] 5.13 49.97 [+ or -] 3.88
mass ([micro]g/
[m.sup.3])
Particle number 6.96 [+ or -] 0.10 10.79 [+ or -] 1.66
(x [10.sup.6]
particles/
[cm.sup.3])
CMD(nm) 26.5 [+ or -] 1.5 27.9 [+ or -] 2.2
GSD 1.60 [+ or -] 0.02 1.65 [+ or -] 0.02
UPASTHMA
Nominal particle 10
mass ([micro]g/
[m.sup.3])
Measured particle 11.08 [+ or -] 3.11
mass ([micro]g/
[m.sup.3])
Particle number 2.20 [+ or -] 0.10
(x [10.sup.6]
particles/
[cm.sup.3])
CMD(nm) 23.1 [+ or -] 1.6
GSD 1.64 [+ or -] 0.01
Abbreviations: CMD, count median diameter; GSD, geometric standard
deviation.
Table 4. Adhesion molecule expression on monocytes and PMNs, UPDOSE
protocol (mean [+ or -] SE, MESF).
Exposure
([micro]g/
[m.sup.3]a) Baseline 0 hr
Monocytes
CD11a Air 64,429 [+ or -] 2,072 62,483 [+ or -] 2,140
UFP 10 63,818 [+ or -] 4,109 59,900 [+ or -] 2,493
UFP 25 62,835 [+ or -] 2,644 56,207 [+ or -] 5,436
CD11b Air 19,034 [+ or -] 986 19,497 [+ or -] 997
UFP 10 17,632 [+ or -] 990 17,287 [+ or -] 1,171
UFP 25 19,056 [+ or -] 1,214 17,769 [+ or -] 922
CD49d Air 14,222 [+ or -] 1,000 13,562 [+ or -] 854
UFP 10 13,634 [+ or -] 1,029 12,587 [+ or -] 694
UFP 25 13,590 [+ or -] 839 12,779 [+ or -] 574
CD54 Air 12,188 [+ or -] 319 13,096 [+ or -] 519
UFP 10 12,541 [+ or -] 469 12,470 [+ or -] 583
UFP 25 13,717 [+ or -] 686 12,591 [+ or -] 584
CD62L Air 43,970 [+ or -] 3,212 34,937 [+ or -] 3,519
UFP 10 38,953 [+ or -] 3,465 30,281 [+ or -] 2,510
UFP 25 41,357 [+ or -] 4,453 33,134 [+ or -] 2,940
PMNs
CD11a Air 28,637 [+ or -] 1,073 28,613 [+ or -] 1,228
UFP 10 29,124 [+ or -] 1,073 26,216 [+ or -] 1,160
UFP25 28,444 [+ or -] 1,397 27,939 [+ or -] 1,151
CD11b Air 18,467 [+ or -] 1,117 18,837 [+ or -] 1,223
UFP 10 16,728 [+ or -] 907 15,997 [+ or -] 1,175
UFP25 19,778 [+ or -] 2,671 15,671 [+ or -] 1,179
CD49d Air 7,422 [+ or -] 593 6,572 [+ or -] 542
UFP 10 7,007 [+ or -] 561 6,172 [+ or -] 559
UFP 25 6,681 [+ or -] 465 6,031 [+ or -] 442
CD54 Air 4,792 [+ or -] 279 4,500 [+ or -] 280
UFP 10 4,953 [+ or -] 271 4,292 [+ or -] 242
UFP 25 4,771 [+ or -] 321 4,084 [+ or -] 216
CD62L Air 66,179 [+ or -] 3,910 59,419 [+ or -] 4,413
UFP 10 60,976 [+ or -] 4,340 57,202 [+ or -] 4,515
UFP 25 66,145 [+ or -] 4,231 60,044 [+ or -] 5,434
Exposure
([micro]g/
[m.sup.3]a) 3.5 hr 21 hr
Monocytes
CD11a Air 62,571 [+ or -] 1,689 65,682 [+ or -] 2,435
UFP 10 59,190 [+ or -] 3,063 65,249 [+ or -] 2,518
UFP 25 59,635 [+ or -] 2,404 63,008 [+ or -] 2,126
CD11b Air 21,076 [+ or -] 1,653 20,901 [+ or -] 1,912
UFP 10 18,335 [+ or -] 1,501 19,391 [+ or -] 1,185
UFP 25 22,059 [+ or -] 4,697 22,669 [+ or -] 3,357
CD49d Air 13,717 [+ or -] 880 13,989 [+ or -] 964
UFP 10 12,946 [+ or -] 706 13,059 [+ or -] 797
UFP 25 12,372 [+ or -] 683 13,542 [+ or -] 935
CD54 Air 13,908 [+ or -] 645 13,307 [+ or -] 823
UFP 10 12,855 [+ or -] 592 13,110 [+ or -] 781
UFP 25 13,533 [+ or -] 856 14,482 [+ or -] 991
CD62L Air 37,600 [+ or -] 3,391 37,399 [+ or -] 3,716
UFP 10 32,409 [+ or -] 1,719 36,356 [+ or -] 3,207
UFP 25 34,676 [+ or -] 3,234 39,168 [+ or -] 4,196
PMNs
CD11a Air 28,793 [+ or -] 1,183 28,867 [+ or -] 1,503
UFP 10 26,260 [+ or -] 985 27,620 [+ or -] 923
UFP25 27,817 [+ or -] 1,137 27,157 [+ or -] 1,411
CD11b Air 21,427 [+ or -] 3,186 21,189 [+ or -] 2,383
UFP 10 16,049 [+ or -] 1,112 21,169 [+ or -] 2,394
UFP25 20,461 [+ or -] 3,457 18,653 [+ or -] 1,760
CD49d Air 6,404 [+ or -] 498 6,098 [+ or -] 686
UFP 10 6,173 [+ or -] 423 6,340 [+ or -] 650
UFP 25 5,677 [+ or -] 446 5,925 [+ or -] 470
CD54 Air 4,586 [+ or -] 246 4,457 [+ or -] 243
UFP 10 4,608 [+ or -] 424 4,435 [+ or -] 213
UFP 25 4,122 [+ or -] 215 4,417 [+ or -] 230
CD62L Air 64,867 [+ or -] 4,303 59,671 [+ or -] 5,970
UFP 10 56,621 [+ or -] 4,636 60,626 [+ or -] 4,180
UFP 25 59,625 [+ or -] 4,296 61,184 [+ or -] 4,054
Exposure
([micro]g/
[m.sup.3]a) ANOVA
Monocytes
CD11a Air
UFP 10
UFP 25
CD11b Air
UFP 10
UFP 25
CD49d Air
UFP 10
UFP 25
CD54 Air Exposure
UFP 10 p = 0.001
UFP 25
CD62L Air Exposure x sex
UFP 10 p = 0.006
UFP 25
PMNs
CD11a Air
UFP 10
UFP25
CD11b Air
UFP 10
UFP25
CD49d Air Exposure x sex
UFP 10 p = 0.007
UFP 25
CD54 Air
UFP 10
UFP 25
CD62L Air
UFP 10
UFP 25
Table 5. Adhesion molecule expression on monocytes and PMNs, UP50
protocol (mean [+ or -] SE, MESF).
Exposure Baseline 0 hr
Monocytes
CD11 (a) Air 65,882 [+ or -] 3,277 66,463 [+ or -] 2,934
UFP 69,090 [+ or -] 3,146 68,680 [+ or -] 2,935
CD11 (b) Air 16,840 [+ or -] 899 20,104 [+ or -] 905
UFP 18,365 [+ or -] 1,153 19,733 [+ or -] 1,206
CD18 Air 62,675 [+ or -] 2,948 68,897 [+ or -] 2,942
UFP 67,246 [+ or -] 2,751 67,175 [+ or -] 2,582
CD49 (d) Air 16,334 [+ or -] 939 16,588 [+ or -] 859
UFP 16,643 [+ or -] 938 16,445 [+ or -] 874
CD54 Air 9,637 [+ or -] 1,431 10,654 [+ or -] 1,668
UFP 10,526 [+ or -] 1,715 11,095 [+ or -] 1,782
CD62L Air 58,551 [+ or -] 3,188 50,197 [+ or -] 3,410
UFP 57,666 [+ or -] 3,519 49,307 [+ or -] 3,261
PMNs
C011 (a) Air 30,921 [+ or -] 851 30,934 [+ or -] 862
UFP 31,569 [+ or -] 1,014 32,158 [+ or -] 1,055
CD11 (b) Air 16,406 [+ or -] 628 18,053 [+ or -] 934
UFP 16,678 [+ or -] 830 19,155 [+ or -] 1,953
CD18 Air 34,919 [+ or -] 1,335 36,961 [+ or -] 1,352
UFP 36,010 [+ or -] 1,032 37,687 [+ or -] 1,810
CD49 (d) Air 6,455 [+ or -] 412 6,345 [+ or -] 264
UFP 6,186 [+ or -] 335 6,252 [+ or -] 330
CD54 Air 8,182 [+ or -] 584 8,339 [+ or -] 484
UFP 8,524 [+ or -] 427 9,071 [+ or -] 545
CD62L Air 87,437 [+ or -] 4,510 88,596 [+ or -] 3,485
UFP 92,053 [+ or -] 4,760 89,783 [+ or -] 4,262
Exposure 3.5 hr 21 hr
Monocytes
CD11 (a) Air 65,658 [+ or -] 2,963 69,888 [+ or -] 2,853
UFP 66,222 [+ or -] 2,696 69,813 [+ or -] 2,835
CD11 (b) Air 19,938 [+ or -] 835 18,728 [+ or -] 1,092
UFP 18,531 [+ or -] 952 18,389 [+ or -] 932
CD18 Air 67,872 [+ or -] 2,780 68,661 [+ or -] 2,749
UFP 66,277 [+ or -] 2,488 67,307 [+ or -] 2,768
CD49 (d) Air 17,371 [+ or -] 954 16,951 [+ or -] 9,571
UFP 17,182 [+ or -] 965 17,282 [+ or -] 909
CD54 Air 11,198 [+ or -] 1,728 9,969 [+ or -] 1,639
UFP 10,889 [+ or -] 1,871 10,352 [+ or -] 1,791
CD62L Air 48,580 [+ or -] 3,027 9,699 [+ or -] 1,557
UFP 50,241 [+ or -] 2,848 56,880 [+ or -] 3,515
PMNs
C011 (a) Air 31,339 [+ or -] 960 31,683 [+ or -] 944
UFP 31,652 [+ or -] 912 31,751 [+ or -] 927
CD11 (b) Air 17,262 [+ or -] 678 17,355 [+ or -] 869
UFP 17,076 [+ or -] 777 18,014 [+ or -] 713
CD18 Air 36,486 [+ or -] 1,286 35,907 [+ or -] 1,226
UFP 36,255 [+ or -] 1,060 35,316 [+ or -] 983
CD49 (d) Air 6,399 [+ or -] 279 6,145 [+ or -] 204
UFP 6,362 [+ or -] 340 6,284 [+ or -] 305
CD54 Air 8,973 [+ or -] 552 8,114 [+ or -] 415
UFP 8,668 [+ or -] 458 8,501 [+ or -] 402
CD62L Air 88,617 [+ or -] 4,056 87,244 [+ or -] 3,362
UFP 90,736 [+ or -] 4,227 89,363 [+ or -] 3,898
Exposure 45 hr ANOVA
Monocytes
CD11 (a) Air 71,292 [+ or -] 2,885
UFP 71,773 [+ or -] 3,132
CD11 (b) Air 18,364 [+ or -] 993
UFP 18,369 [+ or -] 815
CD18 Air 68,963 [+ or -] 3,187 Exposure
UFP 68,754 [+ or -] 3,052 p = 0.0002
CD49 (d) Air 17,126 [+ or -] 1,079
UFP 17,484 [+ or -] 1,167
CD54 Air 9,827 [+ or -] 1,687 Exposure x sex
UFP 10,339 [+ or -] 1,811 p = 0.025
CD62L Air 59,189 [+ or -] 2,271
UFP 58,283 [+ or -] 3,020
PMNs
C011 (a) Air 31,712 [+ or -] 937 Exposure x time
UFP 32,130 [+ or -] 921 p = 0.037
CD11 (b) Air 17,525 [+ or -] 848
UFP 17,545 [+ or -] 694
CD18 Air 35,868 [+ or -] 1,450 Exposure
UFP 35,682 [+ or -] 1,087 p = 0.023
CD49 (d) Air 6,070 [+ or -] 203
UFP 6,114 [+ or -] 258
CD54 Air 8,072 [+ or -] 383
UFP 8,446 [+ or -] 389
CD62L Air 89,489 [+ or -] 2,648
UFP 94,055 [+ or -] 4,598
Table 6. Adhesion molecule expression on monocytes and PMNs, UPASTHMA
protocol (mean [+ or -] SE, MESF).
Exposure Baseline 0 hr
Monocytes
CD11 (a) Air 21,179 [+ or -] 4,120 20,442 [+ or -] 3,989
UFP 32,102 [+ or -] 7,076 30,277 [+ or -] 6,791
CD11 (b) Air 25,022 [+ or -] 2,822 31,626 [+ or -] 5,969
UFP 26,958 [+ or -] 4,112 25,452 [+ or -] 4,611
CD18 Air 85,586 [+ or -] 6,773 87,234 [+ or -] 8,882
UFP 84,999 [+ or -] 7,252 81,131 [+ or -] 7,931
CD49 (d) Air 17,172 [+ or -] 731 16,739 [+ or -] 925
UFP 18,378 [+ or -] 865 16,967 [+ or -] 873
CD54 Air 19,102 [+ or -] 1,386 19,432 [+ or -] 1,430
UFP 20,673 [+ or -] 2,009 20,438 [+ or -] 2,088
CD62L Air 45,571 [+ or -] 2,571 39,446 [+ or -] 2,652
UFP 51,939 [+ or -] 5,305 43,483 [+ or -] 4,955
PMNs
CD11 (a) Air 10,540 [+ or -] 1,775 10,010 [+ or -] 1,771
UFP 14,562 [+ or -] 2,749 14,161 [+ or -] 2,679
CD11 (b) Air 24,078 [+ or -] 2,783 26,353 [+ or -] 3,578
UFP 23,819 [+ or -] 2,343 22,792 [+ or -] 3,224
CD18 Air 48,861 [+ or -] 3,054 47,564 [+ or -] 3,026
UFP 46,982 [+ or -] 2,925 44,465 [+ or -] 2,676
CD49 (d) Air 5,342 [+ or -] 211 5,122[+ or -]2 28
UFP 5,499 [+ or -] 315 4,964 [+ or -] 212
CD54 Air 5,631 [+ or -] 230 5,348 [+ or -] 236
UFP 6,262 [+ or -] 451 5,759 [+ or -] 453
CD62L Air 78,859 [+ or -] 3,812 69,825 [+ or -] 3,978
UFP 79,315 [+ or -] 6,332 75,646 [+ or -] 6,405
Exposure 3.5 hr 21 hr
Monocytes
CD11 (a) Air 19,336 [+ or -] 4,042 21,126 [+ or -] 5,569
UFP 29,592 [+ or -] 6,630 30,468 [+ or -] 6,809
CD11 (b) Air 26,553 [+ or -] 3,319 26,345 [+ or -] 3,456
UFP 25,742 [+ or -] 4,241 24,498 [+ or -] 4,199
CD18 Air 82,899 [+ or -] 6,465 82,697 [+ or -] 7,370
UFP 81,297 [+ or -] 9,950 82,028 [+ or -] 6,767
CD49 (d) Air 16,013 [+ or -] 616 16,627 [+ or -] 837
UFP 17,138 [+ or -] 919 17,715 [+ or -] 877
CD54 Air 18,285 [+ or -] 1,248 19,043 [+ or -] 1,410
UFP 19,861 [+ or -] 1,934 20,014 [+ or -] 1,853
CD62L Air 41,214 [+ or -] 2,703 45,100 [+ or -] 2,847
UFP 42,198 [+ or -] 3,954 46,105 [+ or -] 4,023
PMNs
CD11 (a) Air 10,107 [+ or -] 1,837 10,986 [+ or -] 2,830
UFP 13,790 [+ or -] 2,780 13,765 [+ or -] 2,727
CD11 (b) Air 25,211 [+ or -] 2,533 25,199 [+ or -] 2,072
UFP 25,376 [+ or -] 2,984 22,085 [+ or -] 2,479
CD18 Air 45,449 [+ or -] 2,457 45,303 [+ or -] 2,719
UFP 43,512 [+ or -] 3,174 44,599 [+ or -] 2,862
CD49 (d) Air 5,090 [+ or -] 162 4,805 [+ or -] 248
UFP 4,887 [+ or -] 210 4,783 [+ or -] 234
CD54 Air 5,234 [+ or -] 222 5,433 [+ or -] 277
UFP 5,604 [+ or -] 458 5,535 [+ or -] 399
CD62L Air 71,796 [+ or -] 3,691 72,829 [+ or -] 4,711
UFP 70,468 [+ or -] 4,961 74,971 [+ or -] 5,500
Exposure 45 hr ANOVA
Monocytes
CD11 (a) Air 21,407 [+ or -] 5,550
UFP 29,751 [+ or -] 6,640
CD11 (b) Air 27,703 [+ or -] 3,228 Exposure
UFP 25,814 [+ or -] 3,502 p = 0.029
CD18 Air 85,455 [+ or -] 7,819
UFP 77,346 [+ or -] 7,334
CD49 (d) Air 16,856 [+ or -] 771
UFP 17,327 [+ or -] 879
CD54 Air 19,281 [+ or -] 1,319
UFP 19,284 [+ or -] 1,491
CD62L Air 44,329 [+ or -] 2,870
UFP 45,608 [+ or -] 4,271
PMNs
CD11 (a) Air 11,199 [+ or -] 2,953
UFP 13,710 [+ or -] 2,652
CD11 (b) Air 30,893 [+ or -] 4,350
UFP 22,781 [+ or -] 1,886
CD18 Air 50,312 [+ or -] 5,429
UFP 43,470 [+ or -] 3,006
CD49 (d) Air 4,923 [+ or -] 185
UFP 4,950 [+ or -] 241
CD54 Air 5,635 [+ or -] 239 Exposure x time
UFP 5,660 [+ or -] 398 p = 0.031
CD62L Air 72,429 [+ or -] 4,184 Exposure x sex
UFP 74,541 [+ or -] 5,925 p = 0.011
Table 7. Blood leukocyte marker expression at
baseline that differed between asthmatic and
healthy subjects (mean [+ or -] SE, MESF).
Healthy (a) Asthma p-Value
Lymphocytes
CD11 (a) 41,710 [+ or -] 1,844 14,575 [+ or -] 4,161 < 0.001
CD11 (b) 1,460 [+ or -] 67 1,784 [+ or -] 107 0.017
CD49 (d) 8,168 [+ or -] 335 10,486 [+ or -] 324 < 0.001
CD54 2,381 [+ or -] 69 2,964 [+ or -] 155 0.003
Monocytes
CD11 (a) 64,155 [+ or -] 4,041 26,220 [+ or -] 5,260 < 0.001
CD11 (b) 17,944 [+ or -] 915 25,047 [+ or -] 2,751 0.025
CD49 (d) 13,556 [+ or -] 915 17,089 [+ or -] 642 0.005
CD54 12,314 [+ or -] 401 17,942 [+ or -] 1,065 < 0.001
PMNs
CD11 (a) 28,358 [+ or -] 904 12,753 [+ or -] 2,276 < 0.001
CD11 (b) 16,868 [+ or -] 1,055 24,178 [+ or -] 2,705 0.021
C049 (d) 7,189 [+ or -] 545 5,292 [+ or -] 282 0.007
CD62L 63,591 [+ or -] 4,614 80,656 [+ or -] 5,954 0.032
(a) Includes subjects from UPREST and UPDOSE (n= 24).
Source of some immunofluorescence markers differed for
UP50, resulting in changes in baseline values, so these
healthy subjects were not included.
Table 8. Summary of UFP exposure effects.
Lymphocyte
subsets and Leukocyte
Protocol Adhesion molecules activation counts
UPREST (n=12) No convincing effects No effects No effects
(see text)
UPDOSE (n=12) Decreased monocyte Increased Decreased
CD54 CD[25.sup.+] monocytes
Decreased PMN T and basophils
cells (females) (females)
CD49d (males)
UP50 Decreased monocyte Increased Decreased
(n=16) CD 18 and CD54 CD[25.sup.+] eosinophils
(males) T cells
Decreased PMN CD18
and increased CD11
a
UPASTHMA Decreased monocyte Decreased Decreased
(n=16) CID11b CD[4.sup.+] eosinophils
Decreased PMN CD54 T cells and basophils
and increased CD62L
(males)
Decreased eosinophil
CD11b
|
|
||||||||||||||||||

`kəsīt')
tro·scop
Printer friendly
Cite/link
Email
Feedback
Reader Opinion